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环状 RNA 0002762 通过 miR-375 调控宫颈癌致癌蛋白 YBX1 以调控癌细胞恶性。

Circ_0002762 Regulates Oncoprotein YBX1 in Cervical Cancer via mir-375 to Regulate the Malignancy of Cancer Cells.

机构信息

Department of Gynecology and Obstetrics, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong, China.

出版信息

Protein Pept Lett. 2023;30(2):162-172. doi: 10.2174/0929866530666230104155209.

DOI:10.2174/0929866530666230104155209
PMID:36600625
Abstract

BACKGROUND

Cervical carcinoma (CC) is the third most common cancer among females and the fourth leading cause of cancer-related death, which poses a serious threat to women's health. This study investigated the biological function and mechanism of circRNA circ_0002762 in the malignant progression of CC.

METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_0002762, microRNA-375 (miR-375) and Y-box binding protein 1 (YBX1) mRNA expressions in CC tissues and cell lines. After circ_0002762 was overexpressed in CC cell lines, cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and wound healing assays were executed to probe cell growth and migration. Additionally, the targeting relationships between miR-375 and circ_0002762 or YBX1 3'-UTR were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Western blot was adopted to examine YBX1 protein levels in CC cells.

RESULTS

Circ_0002762 expression was raised in CC tissues and cell lines, and highly expressed circ_0002762 was associated with larger tumor size and lymph node metastasis of CC patients. Circ_0007262 overexpression markedly accelerated the proliferation and migration of CC cells. Besides, miR-375 was revealed to be a downstream target of circ_0002762, and miR-375 overexpression counteracted the promoting effects of circ_0002762 overexpression on CC cell viability and migration. YBX1 was identified as a target of miR-375, and circ_0002762 positively modulated YBX1 expressions through adsorbing miR-375.

CONCLUSION

Circ_0002762 promotes the progression of CC via sponging miR-375 and up-regulating YXB1 expression.

摘要

背景

宫颈癌(CC)是女性中第三常见的癌症,也是癌症相关死亡的第四大主要原因,对女性健康构成严重威胁。本研究探讨了 circRNA circ_0002762 在 CC 恶性进展中的生物学功能和机制。

方法

采用实时定量聚合酶链反应(qRT-PCR)检测 CC 组织和细胞系中 circ_0002762、microRNA-375(miR-375)和 Y 盒结合蛋白 1(YBX1)mRNA 的表达。在 CC 细胞系中转染 circ_0002762 后,通过细胞计数试剂盒-8(CCK-8)、5-乙炔基-2'-脱氧尿苷(EdU)和划痕愈合实验检测细胞生长和迁移。此外,通过双荧光素酶报告基因实验和 RNA 免疫沉淀实验证实了 miR-375 与 circ_0002762 或 YBX1 3'-UTR 的靶向关系。采用 Western blot 检测 CC 细胞中的 YBX1 蛋白水平。

结果

circ_0002762 在 CC 组织和细胞系中表达上调,且高表达的 circ_0002762 与 CC 患者的肿瘤体积较大和淋巴结转移有关。circ_0002762 过表达显著促进了 CC 细胞的增殖和迁移。此外,miR-375 被证实是 circ_0002762 的下游靶点,过表达 miR-375 可拮抗 circ_0002762 过表达对 CC 细胞活力和迁移的促进作用。YBX1 被鉴定为 miR-375 的靶基因,circ_0002762 通过吸附 miR-375 正向调节 YBX1 的表达。

结论

circ_0002762 通过海绵吸附 miR-375 和上调 YXB1 表达促进 CC 的进展。

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